OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.

OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.

Kidney is a highly energy-demanding organ rich in mitochondria. Numerous studies have indicated that mitochondria play a crucial role in maintaining normal kidney function and in the pathogenesis of various kidney diseases. Mitochondrial DNA is the exclusive genome of mitochondria. Damage to mtDNA not only leads to mitochondrial dysfunction and degradation of mitochondrial quality, but also acts as an endogenous inflammatory molecule, activating various inflammatory pathways, which contribute to cellular damage and the progression of kidney diseases. This article reviews the mechanisms of mitochondrial DNA damage and its significant role in triggering inflammatory injury in kidney diseases. Additionally, it summarizes the current research progress on various intervention strategies targeting this type of damage.

Objective:To explore the feasibility of radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-PSMA PET/CT. Methods:Patients were enrolled in this single-arm prospective study from March 2019 to January 2022 in the Second Hospital of Tianjin Medical University. Eligible patients were aged ≤80 years with an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. Based on mpMRI and 68Ga-PSMA PET/CT, patients were diagnosed with highly suspected localized prostate cancer with no evidence of distant lymphatic, bone or visceral metastases. Patients were excluded if they had obvious important organs dysfunction, suspected metastatic lesions or history of other malignant tumor. After fully informed of the surgical risks and possibilities of final pathology, patients received laparoscopic or robot-assisted laparoscopic radical prostatectomy. According to final pathological results, the diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was evaluated. Pathological features were compared between low 68Ga-PSMA PET/CT maximum standardized uptake value (SUV max) group (SUV max<10) and high SUV max group (SUV max≥10). Baseline characteristics were compared between clinically significant prostate cancer (CsPCa) and clinically insignificant prostate cancer (cisPCa) + high grade prostatic intraepithelial neoplasia (HGPIN) patients. Additional analysis of the correlation between baseline parameters and different subgroups including pathological stage, ISUP grades and risk groups were performed in CsPCa patients. Results:31 patients were enrolled. Median age was 68 (ranging 48-79)years old. Median BMI was 25.6(ranging 21.9-31.4)kg/m 2. Median prostate specific antigen (PSA) was 23.5 (ranging 5.6-94.7)ng/ml. Median prostate volume was 37.6(ranging 16.2-127.9)ml. Median PSA density (PSAD) was 0.56(ranging 0.11-2.86)ng/ml 2. Fifteen cases were scored prostate imaging reporting and data system (PI-RADS) 4 and 16 cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 13.3 (ranging 4.6-36.7). All surgeries were successfully accomplished without open conversion. Median postoperative hospitalization time was 5 (ranging 4-7)d. No major complication occurred perioperatively. Recovery of urinary continence was within 6 months in all patients. According to the final pathological results, 1(3.2%) patient was confirmed with HGPIN. 30 (96.8%) patients were confirmed with adenocarcinoma, including 26 (86.7%) patients with CsPCa and 4(13.3%) patients with cisPCa. Among prostate cancer cases, the pathological stage of 11(36.7%) was T 2 and 19(63.3%) was T 3. Four(13.3%) cases were with ISUP grade 1, 7(23.3%) cases were with ISUP grade 2, 7(23.3%) cases were with ISUP grade 3 and 12 (40.0%) cases were with ISUP grade≥4.Two(6.7%) cases were in low risk group, 3(10.0%) cases were in intermediate risk group and 25 (83.3%) cases were in high risk group. Twelve(40.0%) patients had positive surgical margins. Standard pelvic lymph node dissection was carried out in 18 (17 prostate cancer and 1 HGPIN) cases. Sixty-two lymph nodes were dissected and none of them was positive. The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT was 96.8%(30/31) in prostate cancer. Compared to low SUV max group, patients in high SUV max group had higher ISUP grade ( P=0.003) but there was no significant difference in positive surgical margin, seminal vesical invasion or pathological stage ( P>0.05). Among CsPCa patients, 10 (38.5%) cases were scored PI-RADS 4 and 16(61.5%) cases were scored PI-RADS 5. Median 68Ga-PSMA PET/CT SUV max was 14.3 (range 6.1-36.7). Compared to cisPCa and HGPIN patients, a smaller median prostate volume (34.3 vs. 73.0 ml, P=0.006), higher median PSAD (0.70 vs. 0.13 ng/ml 2, P=0.001), higher rates of PI-RADS 5 patients (61.5% vs. 0, P=0.018) and higher 68Ga-PSMA PET/CT SUV max (14.3 vs. 6.1, P=0.001) were found in CsPCa patients. Subgroup analysis showed no significant difference between SUV max and pathological stage (25.5 vs. 13.9), ISUP grades (15.4 vs. 14.4 vs. 14.0) and risk groups (9.7 vs. 14.9) in CsPCa patients ( P>0.05). Conclusions:The diagnostic accuracy of mpMRI and 68Ga-PSMA PET/CT is high in prostate cancer. With efficient communication, radical prostatectomy without biopsy for patients with highly suspected localized prostate cancer diagnosed by mpMRI and 68Ga-PSMA PET/CT is safe.

Objective:To explore the impact of urinary iodine concentration (UIC) on response to 131I treatment in differentiated thyroid cancer (DTC) patients with different risk stratifications. Methods:A total of 181 patients with DTC (75 males, 106 females, age: (44.1±12.5) years), who received the first 131I treatment in Tianjin Medical University General Hospital between January 2018 and February 2019, were retrospectively analyzed. Patients were divided into low- to intermediate-risk and high-risk groups. The treatment response was categorized into excellent response (ER) and non-excellent response (non-ER). Factors being evaluated including age, sex, preablative stimulated thyroglobulin (ps-Tg), UIC, etc. Mann-Whitney U test, χ2 test and logistic regression analysis were used for data analysis. Results:The UIC and ps-Tg in the low- to intermediate-risk group ( n=113) was 111.60(55.80, 204.65) μg/L and 2.08(0.63, 4.91) μg/L, respectively. Compared with the ER subgroup ( n=86), non-ER subgroup ( n=27) had higher UIC and ps-Tg level ( z values: -2.585, -4.511, both P<0.05). In the high-risk group ( n=68), UIC was 115.40(61.23, 167.28) μg/L and ps-Tg was 16.65(4.52, 43.45) μg/L. Compared with the ER subgroup ( n=20), non-ER subgroup ( n=48) had higher ps-Tg level ( z=-4.677, P<0.01), while the UIC was not significantly different between ER and non-ER subgroups ( z=-0.013, P>0.05). The multivariate logistic analysis indicated the ps-Tg level was the significant variable for non-ER in low- to intermediate-risk group (odds ratio( OR)=6.157(95% CI: 1.046-36.227); OR=22.965(95% CI: 3.591-146.857), both P<0.05) and high-risk group ( OR=9.696 (95% CI: 1.379-68.169), P<0.05); a high UIC could be an indicator of non-ER only in the low- to intermediate-risk group ( OR=3.715(95% CI: 1.201-11.488), P<0.05). Conclusions:The non-ER is associated with UIC in the low- to intermediate-risk group; however, UIC does not affect the non-ER in the high-risk group. Higher ps-Tg level is associated with non-ER in patients with low- to intermediate-risk and high-risk DTC.

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective: To compare the ablation efficacy and therapy response with 1.1 GBq and 3.7 GBq ¹³¹I in postoperative patients with low- and intermediate-risk differentiated thyroid carcinoma(DTC). Methods: A total of 190 patients (43 males, 147 females, age: (45.8±11.1)years) were enrolled from July 2016 to July 2017. Among them, 96 patients received 1.1 GBq ¹³¹I and 94 were given 3.7 GBq ¹³¹I. Diagnostic whole-body scan was performed 6 months after ¹³¹I ablation for treatment response evaluation, and the successful rate of ¹³¹I ablation was calculated. χ² test or Fisher′s exact test was used for data analysis. The cut-off value of ⁹⁹Tc^m-pertechnetate uptake for predicting the successful rate of remnant thyroid ablation in 1.1 GBq group was determined by receiver operating characteristic (ROC) curve analysis. Results: The successful ablation rates in 1.1 GBq and 3.7 GBq groups were 79.2%(76/96) and 81.9%(77/94), respectively (χ²=0.229, P>0.05). There was no significant difference in the therapy response between the two groups (χ²=1.371, P>0.05). The successful ablation rate in 3.7 GBq group was higher than that in 1.1 GBq group for patients with stage Ⅲ (5/6 vs 1/7, P=0.029). Moreover, for patients with 5 μg/Lvs 10/13, P=0.038). ROC curve analysis showed the cut-off value of ⁹⁹Tc^m-pertechnetate uptake for prediction of the successful ablation rate in 1.1 GBq group was 0.061 5. Conclusion The low- and intermediate-risk DTC patients with stage Ⅲ disease, 5 μg/L99Tc^m-pertechnetate uptake of remnant thyroid should be given 3.7 GBq other than 1.1 GBq ¹³¹I to obtain a better ablation efficacy.

Objective: To investigate the expression and function of the TNF signaling pathway in the early stage of orthodontic tooth movement with periodontitis and to provide evidence to study the early inflammatory response in patients with periodontitis orthodontic treatment. Methods: Sixteen SD rats were randomly divided into four groups: group A--12 h of orthodontic tooth movement of the bilateral maxillary first molars in rats with periodontitis; group B--periodontitis model of the bilateral maxillary first molars without orthodontic tooth movement; group C--12 h of orthodontic tooth movement of the same teeth in rats with healthy periodontium; group D--control group without operations. The bilateral maxillary first molars and surrounding periodontal tissue of each group were collected for gene chip detection. Pathway enrichment analysis, qRT-PCR and GO (gene ontology) analysis were performed to identify differential genes involved in the TNF signaling pathway. Results : Gene chip results showed that the TNF signaling pathway was significantly upregulated in group A, group B and group C (P <0.01). Among the differential genes involved in the pathway, 28 were upregulated and 5 were downregulated in group A, 12 were upregulated and 4 were downregulated in group B, and 12 were upregulated and 1 was downregulated in group C (P <0.05). The most significant GO items included "response to lipopolysaccharide", "inflammatory response", "positive regulation of NF-κB transcription factor activity", "positive regulation of NF-κB import into nucleus" and "response to hypoxia"(P <0.001). qRT-PCR results showed no significant difference in TNF-α mRNA expression in group C compared with that in group D, TNF-α was upregulated in both groups A and B (P <0.01), and mRNA expression decreased in the following order: group A > group B > group C (P <0.05). Compared with group D, the expression levels of prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 ( IL-6) in groups A, B and C were significantly upregulated (P <0.05), but the expression levels of PTGS2 and IL-6 in group A were lower than those in group B (P < 0.05). Conclusion The TNF signaling pathway is activated in the early stage of orthodontic tooth movement in rats with periodontitis. The pathway products participate in many biological processes and play an important role in the inflammatory response and bone absorption.